[Show abstract][Hide abstract]ABSTRACT: We report the energetics of association in polymeric gels with two types of junction points: crystalline hydrophobic junctions and polymer-nanoparticle junctions. Time-temperature superposition (TTS) of small-amplitude oscillatory rheological measurements was used to probe crystalline poly(L-lactide) (PLLA)-based gels with and without added laponite nanoparticles. For associative polymer gels, the activation energy derived from the TTS shift factors is generally accepted as the associative strength or energy needed to break a junction point. Our systems were found to obey TTS over a wide temperature range of 15-70 °C. For systems with no added nanoparticles, two distinct behaviors were seen, with a transition occurring at a temperature close to the glass transition temperature of PLLA, T(g). Above T(g), the activation energy was similar to the PLLA crystallization enthalpy, suggesting that the activation energy is related to the energy needed to pull a PLLA chain out of the crystalline domain. Below T(g), the activation energy is expected to be the energy required to increase mobility of the polymer chains and soften the glassy regions of the PLLA core. Similar behavior was seen in the nanocomposite gels with added laponite; however, the added clay appears to reduce the average value of the activation enthalpy. This confirms our SAXS results and suggests that laponite particles are participating in the network structure.

[Show abstract][Hide abstract]ABSTRACT: ABA triblock copolymers in solvents selective for the midblock are known to form associative micellar gels. We have modified the structure and rheology of ABA triblock copolymer gels comprising poly(lactide)-poly(ethylene oxide)-poly(lactide) (PLA-PEO-PLA) through addition of a clay nanoparticle, laponite. Addition of laponite particles resulted in additional junction points in the gel via adsorption of the PEO corona chains onto the clay surfaces. Rheological measurements showed that this strategy led to a significant enhancement of the gel elastic modulus with small amounts of nanoparticles. Further characterization using small-angle X-ray scattering and dynamic light scattering confirmed that nanoparticles increase the intermicellar attraction and result in aggregation of PLA-PEO-PLA micelles.

[Show abstract][Hide abstract]ABSTRACT: We have shown that we can significantly modify the nanoscale structure of solution and gels of ABA triblock copolymers in a solvent selective for the mid B block by making simple changes to the stereochemistry of the A block. We have also shown that the length of the A block can be used as an additional variable to further modify and thereby control the sizes of the nanoscale domains formed by these polymers in the presence of the solvent. Our systems are poly(lactide)−poly(ethylene oxide)−poly(lactide) solutions and gels, which have been previously shown to have tunable release characteristics and mechanical properties suitable for applications in tissue engineering and drug delivery. We have performed SANS to understand the self-assembly of these polymers in aqueous solution as a function of block length and stereospecificity of the PLA block as well as polymer concentration. A significant difference in structure and association behavior was seen between polymers made from amorphous d/l-lactic acid as compared to those with crystalline l-lactic acid blocks. In the former case, spherical micelles with radii of 10−14 nm form, whereas the latter forms assemblies of nonspherical “lamellar micelles” with characteristic radii of 11−15 nm and thicknesses of 8−10 nm. In both cases, increasing PLA block length leads to a larger characteristic size. Both polymers form an associative network structure at higher concentrations, leading to gelation.

[Show abstract][Hide abstract]ABSTRACT: Previous work has shown that the stiffness of poly(lactide)-b-poly(ethylene oxide)-b-poly(lactide) [PLA-PEO-PLA] hydrogels can be influenced by crystallinity. Those hydrogels with crystalline PLLA end blocks had a higher storage modulus (up to 1 order of magnitude) than the amorphous equivalents. All the previous work was done with polymers synthesized in the bulk. This paper reports the difference in mechanical properties when two different synthetic techniques are usedsbulk and solution synthesis. Solution-synthesized polymers consistently formed stiffer hydrogels than bulk-synthesized polymers. Further investigation determined the following: crystalline polymers from solution synthesis still form stiffer gels than the amorphous analogues, but not to the extent previously reported; the solution synthesized polymers have narrower distributions, but this alone does not account for the mechanical differences. However, the presence of asymmetric triblock copolymers, which act like an effective diblock copolymer, within the bulk-synthesized materials appears to lower the overall stiffness of the gel. The impact on modulus is much larger for amorphous PLA than for crystalline PLLA end block materials. These findings suggest bulk-synthesized polymers likely have more asymmetric triblock copolymers, that decrease the relaxation time of the system, possibly by lowering the junction lifetime, or lead to dangling ends in the network, which cause a loss in mechanical properties when compared to solution-synthesized polymers.

[Show abstract][Hide abstract]ABSTRACT: We observe large-scale structures in hydrogels of poly(l-lactide)-poly(ethylene oxide)-poly(l-lactide) (PLLA-PEO-PLLA) ranging in size from a few hundred nanometers to several micrometers. These structures are apparent through both ultra-small angle scattering (USAS) techniques and confocal microscopy. The hydrogels showed power law scattering in the USAS regime, which is indicative of scattering from fractal structures. The fractal dimension of the scattering from hydrogels revealed that the gels have large size aggregates with a mass fractal structure over the nanometer-to-micrometer length scales. The aggregates also seem to become more "dense" with an increase in the molecular weight of crystalline PLLA domains. Visualization through confocal microscopy confirms that the gels have a microstructure of interspersed micrometer-sized polymer inhomogeneities with water channels running between them. The presence of micrometer-sized water channels in the hydrogels has very important implications for biomedical applications.

[Show abstract][Hide abstract]ABSTRACT: Control over mechanical properties of hydrogels is of primary importance for the use of these materials in drug delivery and tissue engineering applications. We demonstrate here that crystallinity and block length of poly(lactide) (PLA) can be used to tune the elastic modulus of associative network gels of poly(lactide)–poly(ethylene oxide)–poly(lactide) over several orders of magnitude. Polymers made with crystalline L lactic acid blocks formed very stiff hydrogels at 25 wt% concentration with an elastic modulus that was almost an order of magnitude higher than hydrogels of polymers with a similar molecular weight but containing amorphous D/L-lactic acid blocks. The relaxation behavior and crosslink density of gels are also significantly influenced by crystallinity of PLA and are again a function of PLA block length. Using these variables we can design new tailor-made materials for biomedical applications with precise control over their structure and mechanical properties.

[Show abstract][Hide abstract]ABSTRACT: We have achieved nearly zero order sustained release behavior for periods up to 10-20 days for two hydrophobic drugs, sulindac and tetracaine, from 5wt.% micellar solutions of poly(lactide)-poly(ethylene oxide)-poly(lactide) (PLA-PEO-PLA) triblock copolymer. The effect of PLA block length and crystallinity on the drug release profiles was studied. A series of polymers with constant PEO molecular weight of 8900Da and PLA molecular weight varying in the range of 4100-6500Da were examined. Drug release was found to be much faster for polymers with crystalline PLA blocks as compared to those with amorphous PLA blocks. The drug release rate also depends significantly on the length of the PLA block. Sustained release of sulindac was observed up to 20 days, and for tetracaine up to 10 days. By comparison, release of these drugs without polymeric carriers occurs over 4-6h. This result, along with a proposed mechanism for drug release, suggests that polymer-drug interactions significantly impact release profiles, causing slow and sustained release of the drug.

[Show abstract][Hide abstract]ABSTRACT: Hydrogels of poly(lactide)-poly (ethylene glycol)-poly (lactide) have potential applications in drug delivery and tissue engineering. Control over the structure and rheology of the gels is of fundamental importance for the use of this polymer in medical applications. We have performed a complete rheological and structural characterization of these hydrogels using dynamic mechanical rheology, SANS, and USAXS. These polymers form very stiff hydrogels and the structure and properties of these materials can be substantially modified by varying the crystallinity or degree of polymerization (DP) of the hydrophobic PLA block. We have also created reinforced hydrogels with enhanced mechanical properties by addition of laponite nanoparticles. Our recent studies show that the elasticity of the PLA-PEO-PLA hydrogels can be enhanced by orders of magnitude by addition of small amounts of laponite particles to the hydrogels. It is expected that the triblock copolymer micelles adsorb on the surface of the laponite particles to form additional junctions in the hydrogels leading to enhancement in their elasticity. We verify this hypothesis using DLS and SANS techniques.

[Show abstract][Hide abstract]ABSTRACT: Polymeric materials are important in many medical applications. Regenerative medicine offers the potential to repair or replace damaged tissue and polymers are an essential component of many tissue engineering approaches. Hydrogels have many advantageous properties but, generally, lack robust mechanical properties. At the same time, mounting evidence points to the importance of the matrix modulus when constructing devices. In this context, triblock copolymers made from poly(L-lactide)–poly(ethylene glycol)–poly(L-lactide) have been prepared and formulated into hydrogels. Investigations into their mechanical properties found the elastic modulus to be greater than 10 kPa which is at least one order of magnitude stiffer than previously reported from macromolecules composed of similar monomers. Part of the reason is the presence of crystalline lactide domains. Creating hydrogels with tailored modulus across the kPa range will likely have important ramifications in regenerative medicine.